Clinical Trials Logo

Clinical Trial Summary

This clinical study is a phase 4, single-site, open-label pharmacokinetic (PK) study of IV artesunate in up to 100 Ugandan children 6 months-14 years of age who are diagnosed with severe malaria according to standardized World Health Organization (WHO) criteria (any P. falciparum parasitemia and the presence of danger signs). Participants will receive the standard of care IV artesunate for initial treatment of severe malaria per WHO guidelines: children weighing <20 kg should receive 3.0 mg/kg/dose compared to children weighing =20 kg who should receive 2.4 mg/kg/dose, at times 0, 12, 24, 48 and 72 hours (WHO 2015). Parenteral treatment will be administered for a minimum of 24 hours (irrespective of the patient's ability to tolerate oral medication earlier), after which patients will be evaluated clinically and assessed for ability for oral intake of antimalarials. Children who are able to transition to oral antimalarial therapy will initiate a 3-day course of artemisinin-combination oral therapy per national guidelines. The primary objective of the study is to determine the relationship between DHA exposures following IV artesunate dosing and markers of physiologic dysfunction associated with severe malaria in Ugandan children.


Clinical Trial Description

This clinical study is a phase 4, single-site, open-label pharmacokinetic (PK) study of IV artesunate in up to 100 Ugandan children 6 months-14 years of age who are diagnosed with severe malaria according to standardized World Health Organization (WHO) criteria (any P. falciparum parasitemia and the presence of danger signs). Participants will receive the standard of care IV artesunate for initial treatment of severe malaria per WHO guidelines: children weighing <20 kg should receive 3.0 mg/kg/dose compared to children weighing =20 kg who should receive 2.4 mg/kg/dose, at times 0, 12, 24, 48 and 72 hours (WHO 2015). Parenteral treatment will be administered for a minimum of 24 hours (irrespective of the patient's ability to tolerate oral medication earlier), after which patients will be evaluated clinically and assessed for ability for oral intake of antimalarials. Children who are able to transition to oral antimalarial therapy will initiate a 3-day course of artemisinin-combination oral therapy per national guidelines. Biomarkers of physiologic dysfunction will be quantified at regular intervals, including serum lactate, serum glucose, total and direct bilirubin, bicarbonate levels, Blantyre Coma Score (BCS), creatinine and hemoglobin. These biomarkers will be considered both independently and together as a weighted score to relate to the PK of the active metabolite of IV artesunate, DHA and to efficacy markers that more accurately reflect clinical outcomes. We will also quantify P. falciparum parasitemia using standardized thick blood smear and relate this outcome to DHA dose and exposure for comparison with historical studies. Children 6 months to 14 years of age living in or near Tororo District, Uganda, who are diagnosed with severe malaria and who meet inclusion and exclusion criteria will be enrolled. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05750459
Study type Interventional
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact Matthew Laurens
Phone 14107065328
Email mlaurens@som.umaryland.edu
Status Recruiting
Phase Phase 4
Start date November 29, 2023
Completion date December 30, 2024

See also
  Status Clinical Trial Phase
Recruiting NCT05400655 - Anti-malaria MAb in Kenyan Children Phase 2
Completed NCT02773979 - PfSPZ Challenge in Healthy Malaria-Naïve Adults in the United States Phase 1
Completed NCT03660839 - Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria Phase 2
Terminated NCT00988507 - Dose Ranging Study of Ferroquine With Artesunate in African Adults and Children With Uncomplicated Plasmodium Falciparum Malaria Phase 2
Completed NCT02020330 - Optimising Operational Use of Artemether-lumefantrine Comparing 3 Day Versus 5 Day Phase 3
Completed NCT05816330 - L9LS MAb in Malian Adults Phase 2
Completed NCT02353494 - Efficacy and Safety of Dihydroartemisinin-piperaquine (DHP) for the Treatment of Uncomplicated Malaria N/A
Completed NCT00744133 - Malaria Challenge With NF54 Strain Phase 1
Active, not recruiting NCT05304611 - Anti-malaria MAb in Malian Children Phase 2
Completed NCT03014258 - A Systems Biology Approach to Malaria Immunity Phase 1
Completed NCT03168854 - Trial to Evaluate the Safety, Immunogenicity and Protective Efficacy of Three or Five Administrations of GAP3KO Sporozoites Phase 1
Terminated NCT02497612 - To Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine and Artefenomel in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria Phase 2
Completed NCT00371189 - Adenovirus Vaccine for Malaria Phase 1
Not yet recruiting NCT05025761 - Reducing Malaria Transmission in Forest-going Mobile and Migrant Populations in Myanmar N/A
Completed NCT00379821 - Chloroquine Alone or in Combination for Malaria in Children in Malawi Phase 3
Completed NCT04329104 - Safety and Efficacy of CIS43LS Anti-malaria mAb in Mali Phase 2
Completed NCT03589794 - rCSP/AP10-602 [GLA-LSQ] Vaccine Trial Phase 1
Completed NCT02780154 - PfSPZ Challenge in Non-immune Adults in Baltimore, USA Phase 1
Completed NCT02143934 - Effect of Liver and Blood-stage Treatment on Subsequent Plasmodium Reinfection and Morbidity Phase 4
Completed NCT02663700 - Safety and Immunogenicity of Sanaria's Irradiated Sporozoite Vaccine (PfSPZ Vaccine) in Malaria-Experienced Adults in Burkina Faso Phase 1